In recent years there has been a strong interest in the potential effect of migraine disease on other illnesses. Our understanding of the complex pathophysiology of migraine disease that may underlie nonheadache symptoms and syndromes is currently marked by a long list of comorbid disorders. The connection of migraine to other conditions is at various levels of explanation, ranging from some intriguing clinical observations to accepted criteria as a migraine subtype. This is a snapshot of the level of current knowledge of migraine comorbidities and the significance of this information, but the complexity of this subject will be a challenge for a generation of clinicians and scientists.

Some children have visual disturbances that occur in the absence of, or are out of proportion to, their objective ophthalmological findings. These symptoms reflect a wide range of processes that may be benign or a sign of neurological, systemic, or psychiatric disease. This chapter deals with the neuro-ophthalmologic detection of organic and psychogenic disorders that may manifest as transient or unexplained visual loss, along with other episodic visual disturbances that occur in childhood. In these cases, several formidable problems confront the physician who is trying to reach the correct diagnosis. The descriptions of episodic visual disturbances and hallucinations in children are generally less complex in detail than those in the adult population because children have a limited vocabulary and a limited experiential basis of sensory phenomena to draw upon.

Chronic migraine is a debilitating primary headache disorder associated with high personal, familial, and social impact. The diagnosis is made when there are at least 15 headache days monthly including 8 migraine days per month for at least 3 months. The prevalence is 1.4–2.2% in the population. Among individuals diagnosed with chronic migraine, there may be significant variability in headache days with a potential to remit, remain unchanged, or progress to even greater disability. Most chronic migraine progresses from episodic migraine, with several identified risk factors for chronic migraine and migraine progression. The exact mechanism of chronic migraine is unknown but is associated with an increased cortical excitability, central sensitization, alternations in nociceptive signaling, as well as physiological, structural, and functional brain changes. There is evidence for both nonpharmacological and pharmacological treatment options to restore function. The best currently established pharmacologic evidence for the treatment of chronic migraine is onabotulinumtoxinA and topiramate. Behavioral treatments may improve headache symptoms and comorbidities. Emerging data shows potential benefit for neurostimulation, and large well-designed studies are needed. Multicenter randomized placebo-controlled studies of monoclonal antibodies to the calcitonin gene-related peptide, or its receptor, have demonstrated efficacy, tolerability, and safety. Biomarkers are needed to guide prognosis, treatment response, and clinical trials. The concept and management of refractory chronic migraine is discussed, and clinically meaningful endpoints are reviewed.

The first edition of the Italian diagnostic and therapeutic guidelines for primary headaches in adults was published in J Headache Pain 2(Suppl. 1):105–190 (2001). Ten years later, the guideline committee of the Italian Society for the Study of Headaches (SISC) decided it was time to update therapeutic guidelines. A literature search was carried out on Medline database, and all articles on primary headache treatments in English, German, French and Italian published from February 2001 to December 2011 were taken into account. Only randomized controlled trials (RCT) and meta-analyses were analysed for each drug. If RCT were lacking, open studies and case series were also examined. According to the previous edition, four levels of recommendation were defined on the basis of levels of evidence, scientific strength of evidence and clinical effectiveness. Recommendations for symptomatic and prophylactic treatment of migraine and cluster headache were therefore revised with respect to previous 2001 guidelines and a section was dedicated to non-pharmacological treatment. This article reports a summary of the revised version published in extenso in an Italian version.

Migraine is a brain disorder characterized by a piercing headache which affects one side of the head, located mainly at the temples and in the area around the eye. Migraine imparts substantial suffering to the family in addition to the sufferer, particularly as it affects three times more women than men and is most prevalent between the ages of 25 and 45, the years of child rearing. Migraine typically occurs in individuals with a genetic predisposition and is aggravated by specific environmental triggers. Attempts to study the biochemistry of migraine began as early as the 1960s and were primarily directed at serotonin metabolism after an increase of 5-hydroxyindoleacetic acid (5-HIAA), the main metabolite of serotonin was observed in urine of migraineurs. Genetic and biochemical studies have primarily focused on the neurotransmitter serotonin, considering receptor binding, transport and synthesis of serotonin and have investigated serotonergic mediators including enzymes, receptors as well as intermediary metabolites. These studies have been mainly assayed in blood, CSF and urine as the most accessible fluids. More recently PET imaging technology integrated with a metabolomics and a systems biology platform are being applied to study serotonergic biology. The general trend observed is that migraine patients have alterations of neurotransmitter metabolism detected in biological fluids with different biochemistry from controls, however the interpretation of the biological significance of these peripheral changes is unresolved. In this review we present the biology of the serotonergic system and metabolic routes for serotonin and discuss results of biochemical studies with regard to alterations in serotonin in brain, cerebrospinal fluid, saliva, platelets, plasma and urine of migraine patients.

Several conditions are comorbid with migraine; our review is focused on the relation between migraine, and cerebrovascular and cardiovascular diseases. Despite many studies showed an association between migraine and patent foramen ovale, it is still not known whether its presence might be causal for the migraine pathogenesis and currently its closure cannot be recommended for migraine prevention. On the contrary, conflicting epidemiological data link migraine to arterial hypertension and the use of antihypertensive agents acting on the renin-angiotensin system sounds promising in migraine prevention. A complex bidirectional relation exists between migraine and stroke, and new evidences show a clear association between migraine and coronary heart disease. In both conditions, migraine represents a defined risk factor although the magnitude of the risk varies across the different studies. However, since the risk is low in the general population, it is not possible to identify which migraineurs will develop a cardiovascular or a cerebrovascular event making difficult to apply preventive measures.

Migraine is a recurrent clinical syndrome characterised by combinations of neurological, gastrointestinal and autonomic manifestations. The exact patho-physiological disturbances that occur with migraine have yet to be elucidated; however, cervico-trigemino-vascular dysfunctions appear to be the primary cause.

Despite advances in the understanding of the pathophysiology of migraine and new effective treatment options, migraine remains an under-diagnosed, under-treated and poorly treated health condition. Most patients will unsuccessfully attempt to treat their headaches with over-the-counter medications.

Few well designed, placebo-controlled studies are available to guide physicians in medication selection. Recently published evidence-based guidelines advocate migraine-specific drugs, such as serotonin 5-HT1b/1d agonists (the ‘triptans’) and dihydroergotamine mesylate, for patients experiencing moderate to severe migraine attacks. Additional headache attack therapy options include other ergotamine derivatives, phenothiazines, nonsteroidal anti-inflammatory agents and opioids.

The definition of migraine is mainly descriptive: there is no diagnostic test and no useful biomarker. Migraine attacks are invisible but can present with an encyclopedia of neurological symptoms. Pain is commonly assumed to be the essence of migraine, yet there is no structural lesion correlated to it. It can range from no pain at all to excruciating misery. Still, even in its most disabling form, the pain is only one symptom among many others. Migraine is often accompanied by nausea and hypersensitivity to light and sound. Other symptoms may include speech deficits, mood alterations, neck stiffness, and inability to concentrate. Even this brief excerpt of possible clinical presentations points to the involvement of numerous different brain regions during an attack. Migraine can be seen as a temporary, self-limiting shutdown of the brain’s operating system followed by a restart. Almost any function of the brain can be affected which presents a considerable variability in clinical symptoms from one individual to the next and from one attack to another within the same patient.